Coronary heart disease is responsible for greater than one in six deaths and related healthcare costs well in excess of one hundred billion dollars within the United States alone. Approximately 500,000 of these deaths result from rupture of plaques considered insignificant on an angiographic evaluation - the current gold-standard diagnostic technique. Exacerbating the challenges of diagnosing high-risk atherosclerotic plaques, nearly one third of patients with acute coronary syndrome who undergo revascularization procedures are rehospitalized within 15 months. Therefore, there is a definite and urgent clinical need for an interventional imaging technique that can identify and characterize rupture-prone atherosclerotic plaques, enabling improved diagnosis and treatment guidance during coronary artery interventions. OBJECTIVE: The overall goal of our research program is to transfer a new imaging technology, intravascular photoacoustic (IVPA) imaging, from its current proof-of-concept laboratory setting to the development of a commercially viable clinical imaging modality which is capable of visualizing both morphological and compositional properties of atherosclerotic plaques. The underlying hypothesis of this project is that IVPA imaging provides a safe and economically feasible means of improving patient outcomes without significant change to current interventional protocols. PRELIMINARY DATA: The technical feasibility of imaging lipid-rich regions of atherosclerotic plaques, a hallmark indicato acute coronary event risk, has been demonstrated through the combination of intravascular ultrasound (IVUS) and IVPA imaging using ex vivo human artery samples and in vivo in animal models using prohibitively expensive and low frame rate prototype systems. However, critical commercial and clinical uncertainties which may drastically impact the clinical viability of IVPA imaging remain unaddressed. SPECIFIC AIMS: This project entails the design and assessment of two previously unaddressed risks to the translation of IVPA imaging into the cardiac cath lab. In Specific Aim 1, we will design and build a prototype laser system with an output wavelength and technical specifications suitable for real-time, in vivo IVPA imaging of lipid at an economically feasible price point. In Specific Aim 2, we will utilize the developed real-time laser prototype to characterize IVPA laser-tissue interactions and safety. Measurement of potential bulk or local heating will be complimented by in vitro, ex vivo and in vivo evaluation of photothermal effects within the blood and vascular wall. Together, these studies will address fundamental, and previously unassessed, risks of IVPA imaging, thereby evaluating its commercial viability as a clinical imaging modality for interventional cardiologists.